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Upper gastrointestinal tract hemorrhage (UGIH) remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease (PUD) has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor (PPI) therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non-variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. However, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patients with evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today's medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper endoscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low-risk lesions or admission for further monitoring and treatment in higher-risk lesions. Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severity, and potential treatment of UGIH. Long-term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

Buried Barrett's, or subsquamous intestinal metaplasia (SSIM), is defined as the presence of metaplastic, columnar tissue beneath overlying squamous epithelium. Therefore, SSIM cannot be detected by endoscopic visual examination alone; it is detectable only by tissue biopsy. SSIM can develop in patients with Barrett's esophagus (BE) after chronic pharmacologic suppression of gastric acid; it has been identified before and after endoscopic ablative therapies in cohort studies. It is important to determine the malignant potential of SSIM and the effects of endoscopic therapy for BE on development of SSIM; answers to these questions could affect long-term endoscopic surveillance and ablation strategies for patients with BE., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Cyclooxygenase-2 expression is upregulated in Barrett's esophagus and esophageal adenocarcinoma. Photodynamic therapy using porfimer sodium can result in ablation of dysplasia and intramucosal carcinoma, eradication of Barrett's esophagus, and restitution of squamous epithelium. The aim of this study was to determine the effect of photodynamic therapy on cyclooxygenase-2 expression in esophageal epithelium. Paired pre- and post-photodynamic therapy biopsy samples from the same anatomical levels of 20 individuals who had undergone photodynamic therapy for Barrett's esophagus with high-grade dysplasia and/or intramucosal carcinoma were immunostained using a cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was graded in squamous epithelium, Barrett's esophagus, and neoplasia (if present) as follows: grade 0 (no staining), grade 1 (staining in 1-10% of cells), grade 2 (staining in 11-90% of cells), and grade 3 (staining in >90% of cells). Pre-photodynamic therapy median cyclooxygenase-2 expression was grade 2 (range 1-3) in neoplastic foci and grade 1 (range 1-3) in nondysplastic Barrett's esophagus (P=0.0009 for pairwise comparison). With the exception of a few cells staining in the basal epithelial layers, median cyclooxygenase-2 expression was graded as 0 (similar to controls) in both pre-photodynamic therapy squamous epithelium and post-photodynamic therapy neosquamous epithelium. This was significantly lower when compared to either neoplastic foci (P<0.0001) or nondysplastic Barrett's esophagus (P<0.0001) pre-photodynamic therapy. Notably, in four patients with post-photodynamic therapy recurrent neoplasia, cyclooxygenase-2 expression returned to elevated levels. Cyclooxygenase-2 expression is elevated in Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma prior to photodynamic therapy. Following successful photodynamic therapy, cyclooxygenase-2 expression in neosquamous epithelium returns to a low baseline level similar to that observed in native esophageal squamous epithelium. Post-photodynamic therapy neoplastic recurrence is associated with elevated cyclooxygenase-2 expression. Prospective studies should determine whether cyclooxygenase inhibitors have a role as adjuvant therapy to prevent recurrence of Barrett's esophagus following endoscopic therapy., (© Springer-Verlag 2011)

Background: It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett's esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications., Aims: The aim of this study was to determine whether there has been a shift in age at diagnosis of BE over the past decade. Secondary aims were to determine whether there has been a shift in patient body mass index (BMI) or BE segment length., Methods: An endoscopic database at a tertiary medical center was used to identify all esophagogastroduodenoscopies (EGDs) performed between 1997 and 2007. The cohort was restricted to patients newly diagnosed with BE. Pathology records were reviewed to confirm biopsy findings of intestinal metaplasia (IM)., Results: BE was diagnosed in 378 subjects between 1997 and 2007. Mean age at diagnosis of BE was 60.7 +/- 14.1 years, with mean BMI of 27.4 +/- 5.2 kg/m(2) and mean BE segment length of 4.7 +/- 3.7 cm. Between 1997 and 2007 there was no significant change in mean age at diagnosis, BMI, BE segment length or in proportion of men versus women newly diagnosed., Conclusions: Despite an increase in volume of EGDs performed in an open-access endoscopy unit between 1997 and 2007, there was no appreciable shift in age at diagnosis of BE. BMI and BE segment length among newly diagnosed patients also remained stable over this time period.

The advent of liver transplantation has greatly improved the long-term survival of patients with decompensated cirrhosis, and surgery is now performed more frequently in patients with advanced liver disease. The estimation of perioperative mortality is limited by the retrospective nature of and biased patient selection in the available clinical studies. The overall experience is that, in patients with cirrhosis, use of the Child classification and Model for End-Stage Liver Disease (MELD) score provides a reasonably precise estimation of perioperative mortality. Careful preoperative preparation and monitoring to detect complications early in the postoperative course are essential to improve outcomes.

Background: The management of patients with acute myocardial infarction (AMI) and upper gastrointestinal bleeding (UGIB) can present a challenge. The utility of upper endoscopy (esophagogastroduodenoscopy, EGD) and endoscopic therapy must be weighed against safety considerations., Aim: To assess the utility and safety of EGD in patients with UGIB and AMI., Methods: Using decision analysis, patients with UGIB and AMI were assigned to one of two strategies: (1) EGD prior to cardiac catheterization (EGD strategy) and (2) cardiac catheterization without EGD (CATH strategy)., Results: In patients with overt UGIB, the EGD strategy resulted in 97 deaths per 10,000 patients, compared with 600 deaths in the CATH strategy. The EGD strategy resulted in fewer non-fatal complications (1,271 vs. 6,000 per 10,000 patients). In patients with occult blood loss, the EGD strategy resulted in more deaths (59 vs. 16 per 10,000) and more non-fatal complications (888 vs. 160 per 10,000) than the CATH strategy., Conclusions: Our analysis supports EGD prior to cardiac catheterization in patients with AMI and overt UGIB. This strategy results in fewer deaths and complications compared with a strategy of proceeding directly to catheterization. Our analysis does not support routine EGD prior to cardiac catheterization in patients with fecal occult blood.

Background: Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma., Objective: To identify patient variables that influence the likelihood of response to PDT., Design: A retrospective cohort study., Setting: Tertiary-referral center., Patients: A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer., Interventions: PDT with porfimer sodium., Main Outcome Measurements: (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium., Results: Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone., Limitations: Retrospective study, limited sample size without a control group for comparison., Conclusions: PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure.

Background & Aims: Patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma are at risk of progression to invasive carcinoma. Both esophagectomy and endoscopic ablation are treatment options. The aim of this study was to identify predictors of surgical versus endoscopic therapy at a tertiary center., Methods: An institutional database identified patients with Barrett's esophagus between 2003 and 2007. Demographic data and International Classification of Diseases-9th revision codes for esophagectomy, endoscopic ablation, as well as selected medical comorbidities were retrieved. Individual endoscopy, surgical, and pathology reports were reviewed., Results: Among 2107 individuals with Barrett's esophagus, 79 underwent esophagectomy and 80 underwent endoscopic ablation. The mean age was 63.1 +/- 10.6 years in the surgical group and 69.7 +/- 9.4 years in the ablation group (P < .0001). Among high-grade dysplasia/intramucosal carcinoma patients, 9 of 76 (12%) first seen by a gastroenterologist underwent esophagectomy, whereas 18 of 21 (86%) first seen by a surgeon underwent esophagectomy. In a logistic regression model, factors associated independently with esophagectomy were as follows: patient age of 60 or younger (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.65-14.9), cancer stage T1sm or greater (OR, 16.0; 95% CI, 5.60-45.6), and initial consultation performed by a surgeon (vs gastroenterologist) (OR, 35.1; 95% CI, 9.58-129)., Conclusions: Patient age and cancer stage predict treatment modality for Barrett's esophagus with neoplasia. Treatment choice is influenced further by whether the initial evaluation is performed by a gastroenterologist or a surgeon.

Background: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas., Objective: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients., Design: A pilot feasibility study., Setting: Massachusetts General Hospital., Patients: Twelve patients undergoing routine EGD., Results: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion., Limitations: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses., Conclusions: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.

Background & Aims: The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barrett's esophagus, are associated with post-PDT stricturing., Methods: Data from all patients who had undergone PDT with porfimer sodium for Barrett's esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed., Results: One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007). There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barrett's esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P = .025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barrett's esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length., Conclusions: An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barrett's esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT.

Gastrointestinal bleeding affects a substantial number of elderly people and is a frequent indication for hospitalization. Bleeding can originate from either the upper or lower gastrointestinal tract, and patients with gastrointestinal bleeding present with a range of symptoms. In the elderly, the nature, severity, and outcome of bleeding are influenced by the presence of medical comorbidities and the use of antiplatelet medication. This Review discusses trends in the epidemiology and outcome of gastrointestinal bleeding in elderly patients. Specific causes of upper and lower gastrointestinal bleeding are discussed, and recommendations for approaches to endoscopic diagnosis and therapy are given.

Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is common in patients with HIV infection. HIV infection and immunosuppression alter the natural history of chronic viral hepatitis, and some patients experience accelerated progression to clinically significant liver disease. Therapies used in the treatment of HBV or HCV monoinfection have been applied to the treatment of HIV-coinfected patients. However, development of viral resistance and lack of virologic response remain significant areas of concern. Timely diagnosis and clinical staging of chronic hepatitis infection are critical in the management of HIV-coinfected patients.